Response of central serous chorioretinopathy evaluated by multimodal retinal imaging.

PurposeTo identify predictive biomarkers of treatment outcomes by multimodal retinal imaging in patients affected by central serous chorioretinopathy (CSC).Patients and methodsIn this interventional non-randomized clinical study, 27 treatment-naive CSC patients were prospectively enrolled and treated with oral eplerenone for 5-13 weeks. Primary outcomes included presence of pathological findings on indocyaine green angiography (ICGA), structural optical coherence tomography (OCT) and OCT-angiography (OCT-A) at baseline associated with different response to the treatment.ResultsA total of 29 eyes of 27 patients (2 females, 25 males) met the inclusion criteria and were included in the study (mean age was 45±7 years). Mean CSC duration at baseline was 13.5±4.4 weeks. After a mean of 10.5 weeks of treatment, mean central macular thickness significantly reduced (P<0.001), and mean best-corrected visual acuity improved (P<0.001). Seventeen eyes (61%) demonstrated total reabsorption of subretinal fluid on structural OCT, five eyes (18%) presented a partial response to eplerenone therapy and six eyes (21%) showed no response. The complete response to the treatment was associated with absence of CNV at OCT-A and the presence of hotspot at ICGA (P<0.001 and P=0.002, respectively). None of eight eyes with CNV in OCT-A imaging had a complete response to eplerenone and none of three eyes without hotspot at ICGA showed a complete response to the treatment.ConclusionsMultimodal retinal imaging allowed us to propose predictive biomarkers (ie, absence of CNV on OCT-A and presence of hotspot on ICGA) for treatment outcomes.

Optical coherence tomography analysis of evolution of Bruch's membrane features in angioid streaks.

PurposeTo describe optical coherence tomography (OCT) features in the Bruch's membrane (BM) of eyes with angioid streaks (AS) and evaluate their evolution over the follow-up.Patients and methodsPatients with AS presenting between March 2016 and September 2016 at two tertiary referral centers were consecutively recruited in this study. Eligibility criteria included prior spectral domain (SD)-OCT images, taken at least 3 months before at the same referral center, with automated eye tracking and image alignment modules. Alterations of BM were described and compared to previous scans over the follow-up. Multimodal imaging was used to identify alteration of retinal pigment epithelium (RPE) and choroid.ResultsThirty-two eyes of 16 consecutive patients with AS were included. BM undulations, mostly observed around the optic nerve head, were found in 19 (59.4%) of 32 eyes. BM breaks were found in 31 (96.9%) out of 32 eyes. Evolution of BM undulations into BM breaks was observed in 5 eyes (15.6%). Choroidal neovascularization (CNV) was observed in 12 eyes (37.5%) during follow-up, typically in areas of BM interruption.ConclusionsBM undulations, probably caused by high stretching forces exerted on the BM around the optic nerve head, seem to precede some BM breaks. BM interruptions may be a preferred way for the growth of CNV, which was identified in one-third of our cases.

Unsuspected ileal stenosis causing obscure GI bleeding in patients with previous abdominal surgery--diagnosis by capsule endoscopy: a report of two cases.

Peri-anastomotic ulcerations may occur in patients with previous abdominal surgery. They may present only with obscure GI bleeding. We report two cases in whom capsule endoscopy identified postsurgical stenoses with ulcers as the cause of obscure GI bleeding. Case 1. A 57-year-old male operated on in 1970 for a post-traumatic diaphragm hernia followed by displacement of the caecum in the upper left abdominal quadrant. Case 2. A 32-year-old female with a salpingectomy for tuberculosis (1978) followed by segmental ileal resection for intestinal obstruction. Both patients had undergone extensive work-up including bidirectional endoscopies and enteroclysis with negative results. Capsule endoscopy with the GIVEN diagnostic system was done. Ileal stenoses with mucosal ulcers in dilated prestenotic loops were observed in both cases. The capsule was retained at the stenosis site, requiring ileal resection and anastomosis. Pathology reports showed mucosal ulcers. In case 2, tuberculosis was ruled out by tissue and faecal polymerase chain reaction and culture. Ileal stenoses with prestenotic ulcerations causing GI bleeding may occur in patients with previous abdominal surgery. Capsule endoscopy may clarify the diagnosis and shorten the diagnostic work-up. However, these patients should be warned that capsule retention requiring surgery might occur.

Effects of calcium and vitamin supplementation on colon cell proliferation in colorectal cancer.

Calcium and antioxidant vitamins, such as A, C, and E, have been shown to reduce colorectal epithelial proliferation and thereby to act as possible chemoprotective agents in colorectal cancer. We investigated the effects of an intervention with calcium and vitamins on cell proliferation in the colonic mucosa of patients operated on for colorectal cancer. Patients with resected colorectal cancer Dukes' stage B-C were randomized to receive daily 30,000 IU of axerophthol palmitate (vitamin A) plus 1 g ascorbic acid (vitamin C) plus 70 mg of dl-alpha-tocopherol acetate (vitamin E) and 2 g natural calcium daily or indistinguishable placebo for 6 months. At the time of surgery and after 6 and 12 months of treatment, cell kinetics of normal colonic mucosa were assessed by using proliferating cell nuclear antigen (PCNA). Ninety patients were enrolled and 77 were assessable: 34 in the treatment group and 43 in the placebo group. A significant reduction of mean total PCNA labeling index (PCNALI) was evident in both groups after 6 months (vitamins/calcium, from 16.11 +/- 2.43 to 10.71 +/- 2.81; placebo, from 17.30 +/- 2.63 to 12.53 +/- 3.40). The difference in the percentage of reduction of mean PCNALI between baseline and after 6 months was not statistically significant in the treatment and placebo groups: 34% and 28%, respectively. A second control, 6 months after discontinuation of vitamin and calcium supplementation, showed a further decrease of mean total PCNALI in both groups, but this was not statistically significant. Our randomized trial showed that calcium and vitamin supplementation does not reduce cell kinetics of colon epithelium. Furthermore, this study suggests the need for extreme caution in the interpretation and publication of studies on chemoprotectants in colon cancer without a control group.

Expression of p53 protein and resistance to preoperative chemotherapy in locally advanced gastric carcinoma.

BACKGROUND: Inactivation of the p53 gene has been reported to be associated with resistance to chemotherapy. The authors evaluated the significance of p53 status to the clinical outcomes of patients with locally advanced, unresectable gastric carcinoma (LAGC) who received chemotherapy. METHODS: Thirty chemotherapy-naive patients with LAGC received weekly administration of cisplatin 40 mg/m2, epi-doxorubicin 35 mg/m2, 5-fluorouracil 500 mg/m2, 6S-leucovorin 250 mg/m2, and glutathione 1500 mg/m2. After eight administrations of these agents, patients were assessed for response. Biopsy specimens of primary tumors were analyzed for p53 status using monoclonal antibody Bp53-12. RESULTS: Characteristics of patients were as follows: The median age was 66 years (range, 44-70 years); 18 were males and 12 were females. Eastern Cooperative Oncology Group performance status was 0 for 14 patients and 1 for 16. Histology was intestinal for 13 patients; for 17, it was diffuse. The site of the primary tumor was the cardia in 8 patients, the body of the stomach in 13, and the antrum in 9. The response rate (assessed with CT scan and endoscopy) for patients with p53 negative tumors was significantly higher than for those with overexpression of p53 (71% vs. 12%, P=0.004). CONCLUSIONS: p53 status analyzed before chemotherapy seems to be associated with response to treatment in patients with LAGC. This may provide a useful guide to selecting neoadjuvant chemotherapy for these patients.

Spontaneous lipid peroxidation and sperm metabolism during incubation in media simulating the oviductal microenvironment.

It has been suggested that along the female genital tract spontaneous lipid peroxidation regulates the limit of the lifetime of spermatozoa. We have studied some aspects of rabbit and mouse spermatozoal metabolism during spontaneous lipid peroxidation in the course of the incubation in media which simulate the oviductal environment. The spermatozoa collected at regular intervals after the beginning of incubation were processed for cytochemical detection of cytochrome oxidase, lactate dehydrogenase and glucose-6-phosphate dehydrogenase activities. Quantitative cytochemical assays were made in situ in individual spermatozoa by microdensitometry. The cytochrome oxidase activity significantly decreased in both species because of damage to mitochondrial enzymes and membranes by radical and non-radical products of lipid peroxidation. The change in lactate dehydrogenase activity indicates that under our experimental conditions the lipid peroxidation process damages membrane permeability more markedly in mouse spermatozoa. The glucose-6-phosphate dehydrogenase activity, which should influence the concentration of reduced glutathione through production of NADPH, is more extensively enhanced in mouse spermatozoa than in rabbit spermatozoa. This is in agreement with the fact that in mouse spermatozoa the glutathione system is the major protective defence against oxidative damage while in rabbit spermatozoa it is superoxide dismutase.

Effect of antiviral treatments on the bone marrow in murine aids.

Blood cytopenia is a common feature in HIV infection, occurring in up to 70% of patients with AIDS. Since at present it is not clear to what extent this is intrinsic to HIV infection or due to opportunistic infections and antiretroviral agents we have investigated the long-term effects of conventional and new antiviral drugs on the bone marrow of normal and immunodeficient mice. The results show that azidothymidine (AZT), dideoxycytidine (DDC) and dideoxycytidine 5'-triphosphate (DDCTP) alone or in combination are all effective in inhibiting the expression of the retroviral protein Pr60gag in bone marrow cells. However, DDCTP was the most effective in preventing bone marrow cytopenia. Combined treatments of AZT plus DDCTP result in a reduction in erythroid precursors compared to that resulting from DDCTP administration, while DDC plus DDCTP results in a differential cell count similar to that found in uninfected mice. Thus, the bone marrow in murine AIDS may prove useful as a model for therapy of retroviral infections and for treating blood cytopenias.

Quantitative cytochemical study of some enzymatic activities in preovulatory bovine oocytes after in vitro maturation.

In the present study quantitative cytochemical assays were used to measure some enzymatic activities in situ in bovine meiotically immature oocytes and oocytes matured in vitro, since the special metabolic activity of the growing oocytes may be a pivotal factor in stabilizing the meiotically arrested oocytes. Modifications of this particular metabolism might destabilize the arrested meiosis. Preovulatory oocytes, mostly at the germinal vesicle stage, were obtained by puncturing follicles ranging from 2 to 6 mm in diameter with a hypodermic needle. A group of collected oocytes was incubated in maturation medium CRML 1066 to obtain metaphase II oocytes. Succinate, lactate and glucose-6-phosphate dehydrogenase activities in just collected meiotically immature and in vitro matured oocytes were assayed cytochemically. Microdensitometric measurements were made with a Vickers M85a scanning microdensitometer. Our findings show that: 1) succinate dehydrogenase activity was significantly increased in matured oocytes; 2) lactate dehydrogenase activity was present and very strong in immature oocytes but was detectable in only about 50% of matured oocytes, with significantly lower integrated optical density values; 3) glucose-6-phosphate dehydrogenase activity was very high in immature oocytes but significantly decreased after in vitro maturation; 4) there was no linear correlation between the integrated optical densities of the three enzymatic activities and the diameters of the oocytes. We suggest that the ability to utilize glucose may appear earlier in bovine oocytes than in other species and takes place at the time of maturation.

The bone marrow in murine AIDS.

In order to increase the understanding of blood cytopenias in HIV infection we have investigated the bone marrow in murine AIDS. C57BL/6 mice infected with the LP-BM5 retrovirus show a decrease in cellularity, numerous haemophagocytic histiocytes, a reduction of all erythroid precursor cells, an increase in eosinophil number and an increase in lymphocytes. Immunostaining with an anti-Pr60gag antibody shows that the majority of bone marrow cells express the viral protein. Thus, the bone marrow in MAIDS has many similarities with the bone marrow from patients with advanced AIDS and may prove useful as a model for therapy aimed at treating blood cytopenias.

[Cytochemical study of human sperm metabolism during in vitro capacitation after cryopreservation]. / Studio citochimico sul metabolismo degli spermatozoi umani nel corso della capacitazione in vitro anche dopo crioconservazione.

To study the effects of deep freezing on the energy metabolism of human spermatozoa, we investigated, by cytochemical quantitative methods, cytochrome oxidase and lactate dehydrogenase activities of fresh and frozen human spermatozoa during in vitro capacitation. Fresh and frozen human spermatozoa were incubated in Biggers, Whitten and Wittingham's medium supplemented with 15% heat-inactivated human serum. Both histoenzymological reactions can be quantitated and have been evaluated by microdensitometric method. The results indicate that human spermatozoa depend almost entirely on anaerobic glycolysis during in vitro capacitation and suggest that both aerobic and anaerobic metabolism in spermatozoa are only slightly impaired by freezing-thawing and storage.

Cytophotometric assay of cytochrome oxidase, lactate dehydrogenase and glucose-6-phosphate dehydrogenase activities in human peroxidized spermatozoa.

Human spermatozoa contain appreciable amounts of intracellular glutathione, which has a protective function against peroxidative degradation of spermatozoal polyunsaturated fatty acids by the NADPH-dependent glutathione peroxidase/reductase enzymatic system. The glutathione system provides a basic defense against peroxidative damage, without which the superoxide dismutase system would dominate. Since oxidative damage is said to include enzyme leakage and changes in metabolism, cytochrome oxidase and lactate dehydrogenase activities were used as indicators of the energy metabolism in unwashed and washed human spermatozoa during lipid peroxidation. Lipid peroxidation was induced by aerobic incubation of sperms in the presence of sodium ascorbate and ferrous sulphate. In addition, since NADPH concentrations influence the concentration of reduced glutathione, we studied glucose-6-phosphate dehydrogenase activity as an indicator of pentose phosphate shunt activity, the main source of NADPH. Microdensitometric measurements of the three enzymes were made by a Vickers M85a scanning microdensitometer. We found that the lipid peroxidation process greatly affects the 3 enzymatic activities examined and that seminal plasma protects against the extensive deleterious effects of lipid peroxidation.

Cholesterol embolism of bone marrow clinically masquerading as systemic or metastatic tumor.

A case of cholesterol embolism of bone marrow, concerning the pelvis and lumbar region and clinically masquerading as systemic disease or metastatic tumor, is reported in an 82-year-old man hospitalized for acute onset of reddish purple nodules on the legs and toes, intense myalgia and dorsal vertebral bone pain. The clinical manifestations leading to consideration of a systemic disease or metastatic tumor were the abnormal bone scintigraphic findings of the pelvis and lumbar region, the elevation of serum alkaline and acid phosphatase and the increase of the bone isoenzyme fractions. The diagnosis of cholesterol embolism was explained by the histological findings of bone marrow biopsy which showed microinfarctions of bone marrow with an osteoproductive and reparative process, and presence of cholesterol clefts.

[Splenic hematopoiesis in an experimental model of hemolytic anemia]. / Emopoiesi splenica in un modello sperimentale di anemia emolitica.

The splenic hemopoiesis of rabbits, made anemic with acetylphenylhydrazine, and of control animals was investigated. Pieces of spleen of both groups were fixed in formalin and embedded in paraffin. Paraffin sections, cut 5-7 microns in thickness, were stained with hematoxylin-eosin, Giemsa, Perls' method for tissue iron (hemosiderin), and Perls-Chayen's method for iron stored in the hemoglobin. The erythroid line in the anemic rabbits, showed a marked increase of proerythroblasts and basophilic erythroblasts, while the poli and orthochromatic erythroblasts were less than their precursors. In contrast these cells were more than their precursors in control animals. There was no notable quantitative difference in the mature elements of this line in the anemic animals and in the controls. Megaloblasts and macroblasts were frequently observed in anemic spleens but they were practically absent in the controls. Regarding to other cell lineages, we noted in the anemic spleens many macrophages containing Perls and Perls-Chayen positive material and some megakaryocytes. Our results indicate that the APH-induced anemia stimulate the erythropoietic activity of the spleen in the rabbit, but the reversion of the amplification phase of the differentiation steps reveals that the erythropoietic process is ineffective. The presence of megalo- and macroblasts provide morphological evidence of dyserythropoiesis and the megakaryocytes suggest that under the anemia condition also the platelet regenerating process is stimulated.

Microphotometric study of glucose-6-phosphate dehydrogenase activity in epididymal spermatozoa during spontaneous lipid peroxidation.

Mammalian spermatozoa are highly sensitive to lipid peroxidation and the glutathione peroxidase/reductase system provides an effective defense against oxidative damage to different degree in different species. Rabbit spermatozoa rely on superoxide dismutase as the primary enzymatic defense against lipid peroxidation and contain only low detectable endogenous glutathione reductase activity while in mouse spermatozoa the glutathione system is the major protective enzyme against cell damage by autoxidation. We describe a cytochemical quantitative assay for glucose-6-phosphate dehydrogenase activity in rabbit and mouse spermatozoa undergoing spontaneous lipid peroxidation during in vitro incubation. Microdensitometric measurements were made by a Vickers M85 a scanning microdensitometer at lambda 585 nm wavelength. Our findings suggest that in mouse spermatozoa, the enhanced glutathione reductase and peroxidase activities induced by the spontaneous lipid peroxidation increases NADPH production from the pentose phosphate shunt, while in rabbit spermatozoa, NADPH production is much lower.

[Severe hemorrhagic thrombopenia during epidemic rubella. Description of 2 cases]. / Grave piastrinopenia emorragica in corso di epidemia di rosolia. Descrizione di due casi.

The authors describe two cases of severe hemorrhagic thrombocytopenia during epidemic rubella. They evaluate the pathogenetic mechanisms.

[Thymopentin in a case of autoimmune thrombocytopenia secondary to chronic lymphatic leukemia]. / Timopentina in un caso di piastrinopenia autoimmune secondaria a leucemia linfatica cronica.

The Authors describe a case of chronic lymphocytic leukemia complicated by immune thrombocytopenic purpura. They consider the various causes of thrombocytopenia during lympho-proliferative disorders and underline the different prognostic significance. They evaluate the efficacy of treatment with timopentina.

Cytochrome oxidase and lactate dehydrogenase activities in peroxidized rabbit epididymal spermatozoa.

We report a quantitative cytochemical study on cytochrome oxidase and lactate dehydrogenase activities on rabbit epididymal spermatozoa during spontaneous lipid peroxidation. Our data show that during aerobic incubation both in NTP and KTP media the sperm cytochrome oxidase activity undergoes a significant decrease. The lactate dehydrogenase activity shows different cytochemical patterns in comparison between the two media considered. Such activity significantly increases in rabbit spermatozoa suspended in NTP medium from the first until the sixteenth hour of incubation time. At the following times the lactate dehydrogenase activity significantly declines showing yet until the later times of incubation integrated optical density values fairly high. During the whole period of the aerobic incubation, the spermatozoa suspended in medium KTP show lactate dehydrogenase integrated optical density values which not significantly differ from those of the control in spite of an initial enhancement from the first until the thirteenth hour of the experimental treatment.

Effects of deep freezing on the energy metabolism of bovine spermatozoa during in vitro capacitation: A cytochemical approach.

In order to study the effects of deep freezing on the energy metabolism of bovine spermatozoa, a cytochemical quantitative study was carried out by a microdensitometric method on cytochrome oxidase and lactate dehydrogenase (LDH) activities. These were evaluated in situ on individual frozen-thawed bull spermatozoa collected at different times during in vitro capacitation. The results showed that in bull spermatozoa both the initiation of motility and capacity to fertilize eggs were associated with the anaerobic rather than aerobic glycolysis. The freezing-thawing processes and storage in liquid nitrogen induced a general enhancement of both the enzymatic activities examined. The high ionic strength treatment gave rise to a significant but reversible decrease in both the cytochrome oxidase and LDH activities in the fresh as well as in the frozen-stored sperm. The findings, based on cytochemical observations of energy metabolism of spermatozoa and evaluated during in vitro capacitation, suggest that the respiration and the anaerobic glycolysis of spermatozoa seem to be slightly impaired by the freezing-thawing and storage processes.